Case Management of Suspect Influenza A (H5N1) Infection in Humans

1. Case Management of Suspect Influenza A (H5N1) Infectionin Humans Part 1: Background information on clinical features of avian influenza H5N1

2. Learning Objectives • Recognize clinical features of H5N1 influenza in humans • Understand how information about the patient before onset of illness can help you suspect infection

3. Part 1 Session Outline • Clinical features • Epidemiological Context • Exposure

4. Illness Scenario • Alex sick for three days • Fever • Headache • Cough • Short of breath • Watery diarrhea • No one else sick • Works at poultry farm and handles poultry Question: Is avian influenza the most likely cause of Alex’s symptoms?

5. Clinical Features

6. General Information

7. Signs and Symptoms

8. Laboratory Findings Commonly associated with avian influenza H5N1: • Drop in white blood cell count (lymphocytes) • Mild to moderate drop in blood platelet count • Increased aminotransferases (liver enzymes)

9. Unusual Clinical Manifestations and Outcomes • Knowledge of avian influenza H5N1 infection in humans is still evolving • Unusual symptoms • Southern Vietnam – encephalitis and diarrhea • Disease can progress to ARDS

10. Seasonal Influenza Ear infection, sinusitis Bronchitis, bronchiolitis Pneumonia viral or secondary bacterial Exacerbation of chronic conditions Muscle inflammation Neurologic Disease Seizures Brain inflammation Reye’s syndrome Influenza A (H5N1) in Humans Almost all develop pneumonia Acute Respiratory Distress Syndrome (ARDS) Multiorgan failure Encephalitis Cytokine storms Complications

11. Alex Question: Do you think Alex has signs and symptoms of avian influenza H5N1? Why or why not?

12. Epidemiological Context

13. Exposure to Avian Influenza • Infected poultry, particularly contact with respiratory secretions • Infected wild or pet birds • Other infected animals (e.g., pigs, cats) • Wild bird feces, poultry manure and litter containing high concentrations of virus • Contaminated surfaces

14. Exposures Continued • Under- or uncooked poultry meat or eggs from infected birds • Contaminated vehicles, equipment, clothing, and footwear at affected sites, such as poultry farms with outbreaks • Contaminated air space (e.g., a barn, hen-house, or the air space proximal to barn exhaust fans) • Bodies of water with infected bird carcasses • Close contact with (within 3 feet of) confirmed cases Cultural context can produce unique exposures

15. Alex Question: Do you think Alex may have been exposed to avian influenza H5N1?

16. Using All of The Information

17. Alex’s Situation • 24 year old Alex sick for three days • Fever • Watery diarrhea • Headache • Cough • No one else sick • Alex works on poultry farm where he handles poultry

18. Alex Question: Would you suspect avian influenza H5N1 infection? Why or why not?

19. Part 1 Summary • Individuals with avian influenza H5N1 infection may have non-specific lower respiratory symptoms, or (rarely) none at all • Ask about recent exposure and contact with humans or animals that may have had avian influenza H5N1 infection

20. Case Management of Suspect Human Avian Influenza H5N1 Infection Part 2: Case Management of Suspected Avian Influenza H5N1 Cases

21. Learning Objectives • Testing available for diagnosing • Clinical specimens • Current treatment options • Infection control measures

22. Part 2 Session Overview • Laboratory Testing • Treating Suspected Patients • Infection Control in the Healthcare Setting

23. Laboratory Testing

24. Diagnostics • Avian influenza H5N1 • Specimens for testing • Influenza A • Imaging

25. RT-PCR Detects viral RNA Diagnose H5N1 in humans BSL-2 conditions Results within hours Viral cultures Only in BSL-3 conditions with enhancements Results in 2 – 10 days Serologic Testing Rise in H5N1 specific antibodies Antigen testing only in USDA-approved BSL-3 containment facility Avian Influenza H5N1

26. Clinical Specimens for Testing Influenza A (H5N1) • Lower Respiratory Tract* • Broncheoalveolar lavage • Tracheal aspirate • Pleural fluid tap • Sputum • Upper Respiratory Tract • Nasopharyngeal swab/aspirate • Oropharyngeal swabs * • Nasal Swab * Preferred specimens

27. Clinical Specimens for Testing • Serology • Acute and convalescent serum specimens • Acute collected within 1 week of symptom onset • Convalescent collected 2-4 weeks after symptom onset • Other infections or concurrent illness • Specimens should be collected within 3 days of symptom onset • Collect all possible specimens, serial collection

28. Clinical Specimens for Testing • Autopsy Specimens • Eight blocks or fixed-tissue specimens from each of the following sites • Central (hilar) lung with segmental bronchi • Right and left primary bronchi • Trachea (proximal and distal) • Pulmonary parenchyma from both right and left lung • Major organs • Myocardium (right and left ventricle) • CNS (cerebral cortex, basal ganglia, pons, medulla, and cerebellum) • Organ with significant gross or microscopic pathology)

29. Influenza A • Rapid tests • Many commercial kits available • Results in 15-30 minutes • Low sensitivity • Positive result cannot differentiate seasonal influenza A from H5N1 • Negative result does not rule out H5N1 as diagnosis

30. Laboratory Diagnostics • CDC’s influenza laboratory is nation’s influenza A reference laboratory • Capable of performing additional tests • Immunohistochemical testing • CDC’s Emergency Response Hotline • 770.488.7100

31. Imaging X-ray changes are common in the lungs of avian influenza H5N1 patients • Non-specific changes • Diffuse or patchy infiltrates • Fluid in the space surrounding the lungs • Cavities forming in the lung tissue BBC News. http://bbb.co.uk Saturday, 3 December 2005

32. Avian Influenza H5N1 Chest X-Ray Chest x-ray of an avian influenza H5N1 patient, shown by day of illness Day 5 Day 7 Day 10 Tran Tinh Hien, Nguyen Thanh Liem, Nguyen Thi Dung, et al. New England Journal of Medicine. 18 March, 2004. vol. 350 no. 12. pp 1179-1188.

33. Treating Suspected Cases

34. Treatment Options • Antivirals • Consider age group • Antibiotics • Supportive care

35. Antivirals Neuraminidase Inhibitor • Neuraminidase enzyme breaks bond between infected cell and newly formed virus • Inhibitor prevents enzyme from breaking bond and releasing virus • Virus particles cannot infect other cells

36. Neuraminidase Inhibitor • Two drugs available • Oseltamivir (Tamiflu®) and Zanamivir (Relenza ®) • Should be given as soon as possible • Effective for treatment and prevention • Used for seasonal and avian influenza

37. Oseltamivir Dosage for seasonal influenza Adults: 75 mg twice a day for 5 days Children: <1 year, not recommended < 15 kg - 30 mg twice a day for 5 day >15 kg to <23 kg - 45 mg twice a day for 5 days >23 kg to <40 kg - 60 mg twice a day for 5 days >40 kg - 75 mg twice a day for 5 days

38. Oseltamivir Dosage for avian influenza H5N1 • Best dosage for H5N1 unknown • Longer treatment (7 to 10 days) OR • Higher doses (150 mg) • Begin within 2 days of symptom onset • Dosage for prevention • Once daily for 7 to 10 days after last exposure • Side Effects • Nausea and vomiting • Skin rash

39. Oseltamivir • Effectiveness in seasonal influenza • Reduces influenza symptoms 1 - 3 days • Reduces lower respiratory tract complications, pneumonia, and hospitalization • Cautions- Consider Risk versus Benefits • People with kidney disease (adjust dose) • Pregnant or nursing females • Contraindication • <1 year of age • Hypersensitivity to any component of product • Resistance • Detected in several avian influenza H5N1 patients

40. Zanamivir • Inhaled by mouth via special device • May be used for > 5 years of age • Treatment dosage • Once in morning and night, 5 days • Side effects • Wheezing, and breathing problems

41. Zanamivir • Effectiveness in seasonal influenza • Reduces influenza symptoms 1 - 3 days • Reduces lower respiratory tract complications • Consider Risk vs. Benefit • People with chronic respiratory disease • Pregnant or nursing females • Resistance • Not identified in human H5N1 infections • Active against Oseltamivir resistant H5N1

42. Other Treatments? • Amantadine and Rimantadine • H5N1 resistant in some isolates • Not as effective as neuraminidase inhibitors • Corticosteroids • Low dose for sepsis • Unclear if high dose useful • Risk of side effects • Ribavirin • Ineffective against influenza viruses

43. Treating Children • Different Oseltamivir dosage • Based on child’s weight • Not approved in children <1 year • No aspirin for children < 18 years of age • Use Acetaminophen or Ibuprofen • Children infectious for 21 days after illness • If child cannot remain hospitalized, educate family about infection control

44. Antibiotics • Broad-spectrum • Do not use as a prophylactic • Give empiric therapy for suspected bacterial pneumonia • Secondary bacterial infection therapy • Treat with intravenous antibiotics as recommended

45. Supportive Care Hospital care for suspected or confirmed avian influenza cases should include: • Isolating the patient • Supplemental oxygen and ventilation • Intensive care support for organ failure • Low dose corticosteroids for sepsis

46. Infection Control in Health Care Setting

47. Infection Control Measures • Patients hospitalized for clinical monitoring, diagnostic testing, and antiviral therapy • Droplet and airborne precautions • Negative pressure • N95 masks or more protective • Eye protection (within 3 feet) • Goggles or face shields

48. Infection Control Measures • Standard Precautions • Hand washing before and after contact with patient or potentially contaminated items • Contact Precautions • Gloves and gown worn • Dedicated equipment used • CDC recommendations http://www.cdc.gov/flu/avian/professional/infect-control.htm

49. Managing Corpses • No risk of transmission from dead bodies • Autopsy procedures could result in transmission • Use appropriate protective equipment • You should know • Where corpses may be sent for disposal • Cultural or religious beliefs to respect when handling corpses

50. Part 2 Summary • Important appropriate clinical specimens are collected and tested • Begin treatment with neuraminidase inhibitor immediately! Do not wait!